According to a 2006 World Health Organization report, over 1 billion people worldwide are afflicted with a neurological disorder, and such disorders result in nearly 6.8 million deaths annually. Therapeutic antigen binding peptides, such as antibodies, could be used for treatment of many, if not the majority, of these neurological disorders. However, treatment of neurological disorders using such therapeutic antigen-binding peptides is frequently hampered by difficulties associated with delivering drugs across the blood-brain barrier (BBB).
Although compounds that enhance the delivery of molecules across epithelial cell layers have been discovered, they have generally been shown to be only effective at enhancing the delivery of small molecules. For example, the peptide 4-phenylazobenzyl oxycarbonyl-Pro-Leu-Gly-Pro has been shown to enhance the transport of small molecules across epithelial cell layers, whereas no penetration enhancing effect was demonstrated for macromolecules of 10 kDa and larger (see U.S. Pat. No. 5,534,496; Yen et al. 1995, J Control Release, 36:25-37). Despite being heavily investigated, there is presently no convenient and efficient method for the delivery of therapeutic antigen-binding polypeptides into the CNS.
There is therefore a continuing need in the art for compositions and methods that enhance the specific delivery of therapeutic antigen-binding polypeptides across epithelial layers, in particular to the CNS for the treatment of CNS disorders.